All mass spectrometers use detection systems with limited signal intensity measurement capabilities. If a signal more intense than the detector's upper limit is measured, the detector becomes saturated. The result of saturation is an inability to accurately measure both the signals intensity and location. Detector saturation can result both in reduced data quality, and a reduced ability of an automated mass spectrometer to appropriately set subsequent operating parameters. If the detector is saturated during the course of a prescan measurement, the results will be an underestimation of the number of ions. Any subsequent analytical scan based upon this prescan would be subject to an unintentionally large ion population with the potential of creating undesirable charge effects or further detector saturation.
Time of flight mass spectrometry (TOFMS) allows high resolution, high accuracy, full scan sensitivity spectra to be attained. TOFMS is based upon the principle that ions of different mass to charge ratios travel at different velocities such that a packet of ions accelerated to a specific kinetic energy separates out over a defined distance according to the mass to charge ratio. By detecting the time of arrival of ions at the end of the defined distance, a mass spectrum can be built up.
TOFMS can be operated in a so-called cyclic mode, in which successive bunches of ions are accelerated to a kinetic energy, separated in flight according to their mass to charge ratios, and then detected. The complete time spectrum in each cycle is detected and the results added to a histogram.
One of the primary challenges in TOFMS is to maximize the dynamic range of the device. This is primarily limited by the processing of the signal from the ion detectors: not only must the number of ions arrived be counted, but also the time at which the ions arrive. This data must be obtained and output before the next set of data can be processed.
The earliest TOFMS devices employed analogue to digital converters (ADC) to digitize the output of an amplifier connected to a collector electrode. The collector electrode in turn received electrons generated by one or more microchannel plate electron multipliers when ions impinged thereon. The output of the multiplier was coupled to a transient recorder or a digital sampling oscilloscope.
Although ADC data acquisition systems do not suffer from the drawbacks of time to digital converters (TDC) (see below), the dynamic range of high speed ADCs is still relatively limited.
Typically, the TOFMS uses a time to digital converter (TDC) detector which employs ion counting techniques to allow a mass spectrum to be generated. However a TDC has a dynamic range of one bit, that is, if more than one ion arrives within a TDC time bin, then the TDC only registers a single count. The impact of a single ion is converted to a first binary value, e.g., 1 and the lack of impact is represented as a second binary value (e.g., 0). This data can then be processed via various timers and/or counters.
The advantage of a TDC over the analogue detection technique described above is that the signal output from the electron multiplier in respect of each ion impact is treated identically so that variations in the electron multiplier output are eliminated. There is, however, a limit to the dynamic range of a TDC detector, caused by a so-called dead time associated with ion detection. Dead-time is the time immediately following the recordal of an event (in this case the arrival of an ion) during which no further ion arrivals can be registered. If a subsequent ion arrives within the dead-time it will not be registered, whereas if it arrives after the dead-time, it will be registered. Thus, at higher ion fluxes, the total of ions arriving may be significantly more than the number actually detected.
Dead-time can also be extended by the arrival of a second ion, arriving within the first ion's dead-time and not being counted, yet still adding onto the already existing dead-time of the first ion. Dead-time arises from multiple sources, e.g., pulse width from the electron multiplier, delay within discriminators, and/or the time bin width of the TDC.
Ultimately, dead-time leads to peak distortion, and the observed peak is reduced in absolute height, since fewer ions are registered. The non-registering of ions can also cause mass shifts to occur.
FIG. 1 illustrates how not only does the dead time cause suppression of the area of the peaks, but the peak is shifted. In FIG. 1, shows a plot of the ions counted on the vertical axis and the time bins on the horizontal axis. Curve 110 represents a situation in which all ions that arrive at the TDC detector arrive far enough apart in time such that dead-time is not an issue, and each individual ion is accounted for and counted. The peak intensity is shown by 120, and it occurs at a time of 130. Curve 140 represents a situation in which multiple ions arrive at the TDC detector within the same time bin, where dead-time is an issue, and some individual ions are not counted. The peak intensity is shown by 150, which is lower than 120, and occurs at a time of 160, a point that is shifted in the time domain from that of 130. The shift in the centroid of the peak will ultimately cause an error in the measured value for m/z if left uncorrected.
One solution to the dead-time peak distortion is to keep the ion rates low enough that the peak distortions become negligible. However if the rates are too low, the sensitivity and the dynamic range are compromised, and the final analysis may be difficult to decipher from the noise level. Another solution is to apply statistical corrections to minimize the impact of dead-time, but these are typically only appropriate over a relatively limited range.
Several techniques have been proposed in recent years to address the problem inherent with ADC and TDC ion detection techniques. One technique utilizes a logarithmic (analogue) amplifier arranged in parallel with a TDC and also an integrating transient recorder. The TDC collects data and analyzes it in respect of very small ion concentrations whilst the transient recorder is able to analyze data in respect of much high ion concentrations without saturation. The dynamic range of the data acquisition system overall is thus much larger than that of a traditional TDC without sacrificing sensitivity at lower ion concentrations. However, the problems characteristic of ADC detectors identified above still remain at higher ion concentrations.
An alternative approach to the issues of sensitivity and dynamic range is to employ an array of adjacent but separate equal area anodes, with a separate TDC for each anode. This allows parallel processing of incoming ions, to increase the number of simultaneously arriving ions that are detected and thus to increase the dynamic range. The problem with this is that the increase in the quantity and complexity of the detection electronics increases the cost and, on average, an array of N detectors can only increase the total number of ions detected by a maximum number of N times.
To address this, two anodes of unequal area can be used. This extends the dynamic range of the detector since, with large numbers of a particular ion species arriving at the detector, the average number of ions detected on the smaller anode is small enough to reduce the effects of saturation. The larger anode, by contrast, can detect ions arriving with a lower concentration without an unacceptable loss of accuracy.
Other solutions to this problem include the use of microchannel plate electron multipliers having collection electrodes (anodes) with different surface areas.
Such multiple detector techniques suffer from drawbacks, nevertheless. Firstly, physical cross-talk between the channels is inevitable. Due to the spatial spread of electron clouds created by the electron multiplier, only a part of the cloud may be collected on the smaller anode; similarly partial carry-over of electron clouds from the larger collector can take place. In addition, the close proximity of the anodes causes capacitive coupling between each which in turn increased the likelihood of electronic cross-talk. The multiplier voltage may collapse when very intense ion pulses are received, as is possible in, for example, inductively coupled plasma/mass spectrometry (ICP/MS) and gas chromatography/mass spectrometry (GC/MS). This results in reduced sensitivity for subsequent mass peaks. Finally, the ratio of “effective areas” may depend heavily on parameters of the incoming ion beam (which in turn may depend upon space charge, ion source conditions etc.) which leads to a mass dependence upon the ratio. This problem is particularly pronounced in narrow ion beams such as are produced in orthogonal acceleration TOFMS.
The last problem outlined above can be addressed by employing a multitude of similar collectors after a common multiplier, connecting each collector to a separate TDC channel. Whilst this solution does largely remove the mass dependence upon the ratio of anode areas, it fails to address the other problems with this multiple detector arrangement, and also extends dynamic range only by a factor equal to the number of channels. Thus, this solution can become complex and even then may not be adequate for certain applications such as gas chromatography/mass spectrometry (GC/MS).
Yet another alternative is to employ an arrangement that comprises two channel type electron multipliers in series, together with an intermediate anode. The intermediate anode intercepts the majority of electrons generated by the first multiplier and allows these minority of electrons which are not intercepted to be captured by the second electron mulitiplier. The analogue amplifier generates a first detector output for the anode, and a discriminator and pulse counter generates a second detector output from the second electron multiplier. The outputs of the two detectors are then combined. Once again, this technique suffers from physical and electronic cross-talk.
In operation of a TOFMS, therefore, the operator has to deal with the competing goals of delivering as high an absolute ion rate as possible to the TOFMS, for best sensitivity, but not so high as to saturate the detection system. When dealing with internal mass standards for high mass accuracy measurements, this problem is further compounded by the need to match closely the relative intensities of the internal standard and the analytes of interest.